Brain tumors and leukemia are the most common children and adolescent malignancies in the U.S. Adequate information on the role of inherited genetic susceptibility and environmental exposures in the development of neoplasms in children and adolescents is lacking. In Taiwan, four large petrochemical industries are located in Kaohsiung metropolitan area. These facilities are proximal to residential areas because of the high population density in the region. Data have shown that the concentrations of ambient polycyclic aromatic hydrocarbons (PAH) and volatile organic compounds (VOC) around the petrochemical industries are at least 10 and 2 times, respectively, higher than those in U.S. industrialized communities. Our preliminary case-control study in Kaohsiung metropolitan showed that young residents (< 30 yr) living within 3 kilometers (km) of the vicinity of petrochemical industries have a 6.0 fold increase in brain neoplasms and a 2.9 fold increase in leukemia. The purpose of this proposal is to examine the association of exposure to air contaminants (PAH & VOC) emitted from the petrochemical industries, specific genetic polymorphisms (P4501A1 (MspI & exon 7) and GSTMI & Tl) from study subjects and their parents, and the risks of brain tumors and leukemia among children and youths in metropolitan Kaohsiung. Our hypothesis is that there is an increase risk of brain tumors and leukemia in patients with higher cumulative exposure to these hazards, and that heritable polymorphisms in several genes modify this association. In addition to an independent association of environmental and genetic factors with brain neoplasm and leukemia, we hypothesize that there is greater risk associated with the presence of combined environmental exposure and the high risk genotype. We also assess the role of the parental genetic polymorphisms in the development of cancer in their sibling. This proposed study uses an environmental molecular epidemiologic approach, utilizing prospective enrollment of a cohort of brain tumor and leukemia subjects and a population-based case-control design. This proposal is responsive to the recommendation of the National Research Council that risk assessment and public health policy pay special attention to the protection of children.